The objective of this project is to investigate the mechanisms by which the cell-mediated immune response (CMI) in the lung is impaired by severe protein-calorie deficiency (PCM). A well-defined rat model will be used to study the effects of PCM on host defenses against aerosolized L. monocytogenes, a prototype of an organism handled by cell-mediated immunity. The specific aims are to determine: 1) whether PCM impairs alveolar macrophage (AM) antigen recognition and antigen presentation to lymphocytes; 2) whether PCM affects the phenotypic populations of resident lymphocytes in lung and spleen, or the changes in these populations which occur after inhalation of a bacterial antigen (L. monocytogenes); 3) whether PCM impairs interleukin-1 production by AM and splenic macrophages; 4) whether PCM impairs interleukin-2 production by T lymphocytes, or whether PCM impairs the lymphocyte proliferative response to interleukin-2; 5) whether PCM affects AM and splenic macrophage activation; 6) whether PCM impairs the generation of AM of inflammatory mediators derived from arachidonic acid; 7) whether resistance to L. monocytogenes in protein-deficient animals can be restored by adoptive transfer of macrophages and/or lymphocytes from listeria-exposed normal animals. Before and after listeria exposure in control, pair-fed and PCM animals, measurements will be made of macrophage antigen presentation to lymphocytes, interleukin-1 an interleukin-2 production, macrophage activation, and macrophage arachidonic acid metabolism. Pulmonary and splenic macrophages and lymphocytes will be used to compare regional responses in the lung with systemic responses. Adoptive transfer experiments will be performed to determine the combinations of cell populations necessary to reconstitute the immune defenses of the PCM animals. This project will yield information about the mechanism(s) by which PCM, a host factor which is common worldwide, affects the expression of cell-mediated immunity within the lung.